Abstract

The host dNTP hydrolase SAMHD1 acts as a viral restriction factor to inhibit the replication
of several retroviruses and DNA viruses in non-cycling human immune cells. However,
understanding the physiological role of mammalian SAMHD1 has been elusive due to the
lack of an animal model. Two recent studies reported the generation of samhd1 knockout mouse models for investigating the restriction of HIV-1 vectors and endogenous
retroviruses in vivo. Both studies suggest that SAMHD1 is important for regulating the intracellular dNTP
pool and the intrinsic immunity against retroviral infection, despite different outcomes
of HIV-1 vector transduction in these mouse models. Here I discuss the significance
of these new findings and the future directions in studying SAMHD1-mediated retroviral
restriction.